As part of a collaborative project affiliated with psychobiologists and psychopharmacologists at the National Institute on Drug Abuse, Intramural Research Program the specific aim of this research is to design and synthesize new tropane analogs which exploit recently proposed new binding sites or binding domains of the cocaine receptor on the dopamine transporter in hope of finding a cocaine antagonist for the potential development of new cocaine medications. These medications could be useful for the treatment of cocaine addiction and drug overdose. A program of chemical synthesis and pharmacologic evaluation will be employed to accomplish these aims. The initial approach for achieving the specific aims of this research will be to affect the stereoselective syntheses and the pharmacologic evaluation of the proposed target benztropine analogs. The tropane analogs will first be tested in in vitro paradigms for receptor affinity and for the ability of the compounds to inhibit dopamine, serotonin and norepinephrine uptake mechanisms. The pharmacologic activity of high affinity ligands will then be determined in vivo by assessment of the stimulation effects (locomotor stimulation, discriminative stimulus effects and reinforcing effects) of the drugs.